Developpement, Reparation et Vieillissement Cerebral

Responsables Jean MARIANI et Rachel SHERRARD

This team studies the mechanisms underlying development, repair, and ageing of the brain, using cerebellar and hippocampal models both in vivo, ex vivo organotypic culture and in vitro to address the fundamental biological bases of these phenomena but also to explore clinical applications.
In addition to exploring genes and signaling pathways that allow selective synapse stabilization during olivocerebellar development and promote appropriate post-lesion repair, we investigate the roles of different proteins associated with Alzheimer’s disease to understand early hippocampal synaptic dysfunction during this ageing-related pathology. At the same time we also study early synaptic changes throughout life (young/adult/aged), in particular the formation, maintenance and disruption of homeostatic synaptic plasticity, which is necessary to maintain the functional stability of neural circuits while, at the same time, allowing their flexibility. .
We are also interested in extra-neuronal factors that impact upon neuronal function, stability and repair. First we study the role of transcription factors, particularly ROR?, in diverse mechanisms of neuroinflammation and neuroprotection and how these may impact on synaptic function and stability. Secondly, we aim to use non-invasive methods (psychomotor stimulation; pulsed magnetic fields – also called rTMS) using our cerebellar model to optimize maintenance and protection of synaptic circuits in the damaged or ageing brain,. This builds on our expertise in in psychomotor and rTMS stimulation with which we have induced structural repair in an abnormal neural circuit. Moreover, with our industry partner we will continue to develop this technology to optimize its application to brain repair. Finally, we extend our exploration of normal and pathological neurological ageing to a new complete test of cognitive function and especially of episodic memory. This test will be optimized and then applied to ageing patients to provide early appropriate diagnosis of cognitive dysfunction, allowing early therapeutic intervention. .
The team’s multidisciplinary approach, from molecules to behavior and bench to the clinic, expands the Unit’s research fields into the evolution of accumulating synaptic dysfunction with time and the potential for its repair.